The proposed research will examine certain aspects of polybrominated biphenyls (PBB) toxicity which occured in Michigan following human exposure, by investigating in detail minor PBB components. Other than the major PBB component, six PBB congeners with known structure are present in PBB and are detectable in human tissue samples. In addition, we have observed more than 25 unidentified minor (0.04-1%) components in PBB and in human tissues. Some of these PBB congeners have been reported to be more toxic, in animal studies, than the major PBB component. Adipose and serum samples for three populations, representing over 2500 individuals, have been previously analyzed for the major PBB component. PBB congeners can be estimated in these samples by reevaluation of existing chromatographic data and by reanalysis aimed at greater specificity and sensitivity, using appropriate standards and high resolution gas chromatography, of stored sample extracts. The three populations span six orders of magnitude of exposure, from low-level general population to highly exposed chemical workers and farm residents. Samples from farm residents (939) and chemical workers (55) were obtained in 1976, and 250 of these persons were restudied in 1978-1980 enabling investigation of changes over time. Samples from a random survey of the Michigan general population (1681) were obtained in 1978. (1) The relation of PBB congener concentrations to clinical findings which have been obtained in previous studies will be explored. (2) Possible synergistic interaction of PCBs and DDE (inevitably present in human tissues) with PBB has been speculated. DDE has been measured in all samples: PCBs have not yet been analyzed in farmers. DDE, PCB, and PBB congeners will be evaluated with respect to clinical findings already recorded in these populations, including serum biochemistry, urinary porphyrins, antipyrine half-life and neurological symptoms, using multivariate statistical methods. (3) Aspects of body storage and metabolism of PBB congeners will be investigated by study of congener concentration and adiopose-serum partition and their changes over time. Preliminary results and analogous studies with PCB congeners in humans indicate a clear relationship of these parameters with storage and elimination of PCBs and PBBs. (4) Metabolism will be investigated by analysis of samples for lower brominated biphenyls some not present in PBB which we have observed in human tissues.